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Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries

2021-01-12Journal article Restricted access
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dc.contributor.authorFutema, Marta
dc.contributor.authorRamaswami, Uma
dc.contributor.authorTichy, Lukas
dc.contributor.authorBogsrud, Martin P.
dc.contributor.authorHolven, Kirsten B.
dc.contributor.authorRoeters van Lennep, Jeanine
dc.contributor.authorWiegman, Albert
dc.contributor.authorDescamps, Olivier S.
dc.contributor.authorDe Leener, Anne
dc.contributor.authorFastre, Elodie
dc.contributor.authorVrablik, Michal
dc.contributor.authorFreiberger, Tomas
dc.contributor.authorEsterbauer, Harald
dc.contributor.authorDieplinger, Hans
dc.contributor.authorGreber-Platzer, Susanne
dc.contributor.authorMedeiros, Ana M.
dc.contributor.authorBourbon, Mafalda
dc.contributor.authorMollaki, Vasiliki
dc.contributor.authorDrogari, Euridiki
dc.contributor.authorHumphries, Steve E.
dc.date.accessioned2022-03-23T17:14:39Z
dc.date.available2022-03-23T17:14:39Z
dc.date.issued2021-01-12
dc.description.abstractBackground and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. Results: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). Conclusions: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.pt_PT
dc.description.abstractHighlights: LDLR mutations are the most common cause of familial hypercholesterolaemia (FH) in children from 8 European countries; Overall, 279 different LDLR mutations were found in 2531 FH children; The frequency of APOB p.(Arg3527Gln) varied significantly over the 8 countries; APOB-FH was less severe than LDLR-FH for low density lipoprotein-cholesterol (LDL-C) concentration and family onset of coronary heart disease (CHD).pt_PT
dc.description.sponsorshipThe European Register is supported by a grant from the International Atherosclerosis Society (Pfizer number 24052829). The UK register is supported by funds from the British Heart Foundation (BHF); HEART UK, Cardiac Network Co-ordinating Group Wales and the Royal College of Physicians. SEH is a BHF Professor and is funded by PG08/008, and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. MF is funded by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no. 14 CVD03). MV is supported by the Ministry of Health, Czechia, project No. 64165, General University Hospital in Prague. TF and LT are supported by the Ministry of Health, Czechia, grant number NU20-02-00261. The Austrian FH register has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Portuguese FH Study has been supported by grants from the Portuguese Science and Technology Foundation and grants from the Portuguese Cardiology Society. AMM was supported by the Portuguese Science and Technology Foundation, grant number SFRH/BD/113,017/2015. The study sponsors had no role in study design, the collection, analysis, and interpretation of data, the writing of the report or the decision to submit the manuscript for publication. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAtherosclerosis. 2021 Feb;319:108-117. doi: 10.1016/j.atherosclerosis.2021.01.008. Epub 2021 Jan 13.pt_PT
dc.identifier.doi10.1016/j.atherosclerosis.2021.01.008pt_PT
dc.identifier.issn0021-9150
dc.identifier.urihttp://hdl.handle.net/10400.18/7993
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/European Atherosclerosis Societypt_PT
dc.relatione_FH. The role of epigenetics in Familial Hypercholesterolaemia phenotypes - towards a more precise medicine
dc.relation.publisherversionhttps://www.atherosclerosis-journal.com/article/S0021-9150(21)00008-3/fulltextpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectHeterozygous Familial Hypercholesterolaemiapt_PT
dc.subjectMutation Spectrumpt_PT
dc.subjectLDL-C Concentrationspt_PT
dc.subjectStatin Treatmentpt_PT
dc.subjectEuropept_PT
dc.subjectPortugalpt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titleComparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countriespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlee_FH. The role of epigenetics in Familial Hypercholesterolaemia phenotypes - towards a more precise medicine
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F113017%2F2015/PT
oaire.citation.endPage117pt_PT
oaire.citation.startPage108pt_PT
oaire.citation.titleAtherosclerosispt_PT
oaire.citation.volume319pt_PT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication86ef85c5-4329-4309-9bd5-6acd1938ea2c
relation.isProjectOfPublication.latestForDiscovery86ef85c5-4329-4309-9bd5-6acd1938ea2c

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